The proposed research is concerned with the biochemical dissection of morphogenesis. Four major systems are under investigation. (a) The retino-tectal projection in the chick embryo. Using in vitro assays for cell recognition between retinal cells and tectal surfaces, cell surface moieities are selectively destroyed with lytic enzymes and the effects on recognition are evaluated. One morphogenetically-active compound has been identified, so far, as the ganglioside GM2. (b) The role surface glycosyltransferases in chick embryo morphogenesis will be tested by specific perturbation of the enzyme classes. Preliminary data suggest that such interference leads to predictable classes of morphogenetic defects. (c) In order to gain further understanding of the biochemistry of the glycosyltransferases, the liver conjugating enzymes are being investigated. These glucuronyltransferases are advantageous for study because they are easily assayed, they are inducible in the chick embryo, with induction, they appear first in the internal cell membranes and, later, on the cell surface and, finally, genetic defects for some of these enzymes are available in the rat and human. (d) Neural crest cells from wild-type and crest-defective mouse mutations will be grown on substrates of hyaluronic acid and chondroitin sulfate in order to test and compare their abilities to migrate on, and spontaneously glycosylate, these substrates. Preliminary experiments with patch and dominant spotting mutants show marked differences in both these parameters.